High-risk Gestational Trophoblastic Neoplasia Research Articles

Curative effects and influenced factors of EMA-CO as an initial regimen for the treatment of high-risk gestational trophoblastic neoplasia

Objective: This study aims to evaluate the efficacy of EMA-CO as an initial regimen for high-risk gestational trophoblastic neoplasia and to analysis the influenced factors. Methods: A total of 81 patients with high-risk gestational trophoblastic neoplasia (HRGTN) treated in Women Hospital Affiliated Zhejiang University from Jan 2007 to Jan 2017 whose primary chemotherapies were EMA-CO were enrolled.The International Federation of Gynecology and Obstetrics (FIGO) prognosis score of all the patients was ≥7.The relationships of different factors were analyzed by univariate and multivariate analysis. Results: Fifty-five of 81 patients (67.90%) achieved complete primary remission with single EMA-CO regimen, 12 patients (14.81%) achieved complete primary remission with EMA-CO regimen and surgery, and 14 patients (17.28%) achieved drug resistance.The univariate and multivariate analysis showed that the FIGO score (P=0.004, OR 1.336, 95%CI 1.099-1.623) was an independent predictive factor for the outcome of EMA-CO regimen. Conclusions: EMA-CO is the first-line regimen used to treat patients with HRGTN. Salvage therapies such as EMA-EP regimen and adjuvant surgery are still effective treatments. The FIGO score is an independent risk factors for the outcome of EMA-CO regimen.

Outcome of treatment with EMA/EP (etoposide methotrexate and actinomycin-D/ etoposide and cisplatin) regimen in gestational trophoblastic neoplasia.

Background: Gestational trophoblastic neoplasia (GTN) originates from placental trophoblast and is a highly chemosensitive and curable gynecologic malignancy. The present study was conducted to evaluate the effectiveness and safety of EMA/EP (etoposide, methotrexate, actinomycin-D, etoposide, and cisplatin) regimen in the treatment of high-risk GTN as well as patients’ outcome. Methods: Hospital charts of all patients with confirmed diagnosis of high-risk GTN who received EMA/EP regimen treatment during a 12-year period (2001-2012) at the tertiary center of comprehensive women's hospital in Tehran, Iran, were reviewed from 2012 to 2013, retrospectively. Results: In this study, 25 patients with GTN who were treated with EMA/EP regimen during the study were identified. Complete remission rate in GTN patients with failure of single agent chemotherapy who were treated with EMA/EP regimen, as the first- line treatment, was 100%, while it was 81% in those with primary high-risk GTN. Overall remission rate in high-risk GTN patients treated with EMA/EP regimen was 88%. Anemia (92%) and leucopenia (72%) were the most common adverse effects of EMA/EP chemotherapy regimen. Acute myeloid leukemia (AML) and mortality, as the most severe adverse effects of EMA/EP regimen, were seen only in 1 patient. Conclusion: According to the results, EMA/EP regimen could induce complete remission in 88% of patients with high-risk GTN. Application of EMA/EP is recommended as the first- line therapy in patients with failure of single agent chemotherapy. However, proper care should be considered to prevent and reduce EMA/EP hematologic toxicity.

Update on the diagnosis and management of gestational trophoblastic disease.

Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow-up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histology type and regression rate. Low-risk GTN (FIGO Stages I-III: score <7) is treated with single-agent chemotherapy but may require additional agents; although scores 5-6 are associated with more drug resistance, overall survival approaches 100%. High-risk GTN (FIGO Stages II-III: score >7 and Stage IV) is treated with multiple agent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent resistant tumors.

A comprehensive analysis of gestational trophoblastic neoplasia trials posted at online clinical trial registries

ObjectiveWe conducted a comprehensive analysis of gestational trophoblastic neoplasia (GTN) trials posted at online registries and aimed to provide useful information for future GTN trial designs. Study designWe searched ClinicalTrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Portal (ICTRP) Search Portal, Australian New Zealand Clinical Trial Registry, ISRCTN Register, and Chinese Clinical Trial Register for all the clinical trials reporting GTN treatments. The general information of each trial was extracted. ResultsTwenty trials meeting the inclusion criteria were included in the final analysis. In total, 6 trials were phase II trials, 2 were phase II/III trials, 7 were phase III trials, and 1 was a phase IV trial; and the phase type of 4 trials were not reported. The conditions included low-risk GTN (n = 15), high-risk GTN (n = 2), and mixed GTN (n = 3). Randomization was performed in 15 trials, and the remaining 5 trials were single-arm trials. The median enrollment size for randomized clinical trials (RCTs) and single-arm trials was 80 and 38, respectively. Among the RCTs, parallel assignment was used in 12 trials, crossover assignment was used in 1, and the intervention models of 2 were not reported. For masking, 15 trials were open-label, 2 were single-blinded, 2 were double-blinded, and the masking status of 1 was not reported. Ovarian functions and pregnancy outcome after chemotherapy were evaluated in only 2 trials. Regarding sponsorship, 2 trials had industry sponsorship. ConclusionConducting RCTs for GTN is challenging, and international collaboration and smarter clinical trial designs are required for future GTN trials.

Application of chest CT scan in gestational trophoblastic neoplasia with lung metastasis

Objective: To explore the role of CT scan for the diagnosis of lung metastasis in stage Ⅲ gestational trophoblastic neoplasia (GTN) . Methods: To figure out the role of CT scan for lung metastasis in GTN initial diagnosis, treatment and follow-up, 93 GTN patients with lung metastasis from January, 2015 to December, 2016 were retrospectively analyzed in Obstetrics and Gynecology Hospital of Fudan University. Results: (1) Among 93 GTN patients with lung metastasis, 70 patients with the International Federation of Gynecology and Obstetrics (FIGO) score ≤6 were defined as low risk GTN and 23 patients score score ≥7 were defined as high risk GTN. Forty nine patients had negative chest X-ray findings and 39 cases with pulmonary lesions were identified both by chest X-ray compared to CT scan. Five cases were excluded due to no consensus could make for the results of chest X-ray. The true positive rate of chest X-ray for lung metastasis were 41% (29/70) in low risk GTN and 43% (10/23) in high risk GTN patients without statistical difference (χ(2)=0.090, P=0.925) . For those patients with positive chest CT scan and negative chest X-ray finding, pulmonary lesions in 32 (65%, 32/49) cases were blocked by heart, chest wall or diaphragm in chest X-ray. Seventeen (35%,17/49) patients with lung lesions less than 5 mm had negative chest X-ray results due to the lower sensitivity compared to CT scan. (2) In 88 patients with stage Ⅲ, 78 patients had successful initial treatment, but 4 of them were recurrence in twelve months follow-up. Ten patients were chemotherapy resistance for the initial treatment. The initial chemotherapy remission rate in low risk GTN patients was higher than that in high risk ones (χ(2)=4.911, P=0.027) . In 49 cases with negative chest X-ray, there was no correlation with the rate of remission,chemotherapy resistance and recurrence in stage Ⅲ patients (P>0.05) . (3) For those patients who had poorly response to initial chemotherapy, the diameters of lesions in lung were unchanged or increased during the treatment, form (5.1±4.1) mm to (7.4±2.8) mm. The pulmonary lesions were continuously shrunk from (7.8±5.3) mm to (4.7±4.4) mm for those patients with complete and partial remission including the recurrent GTN patients (Z=-2.713, P=0.007) . Conclusions: Patients with GTN in stage Ⅲ have down staging if only use chest X-ray for imaging at the initial diagnosis. Chest CT scan is recommended for primary imaging evaluation of FIGO staging in qualified medical organization. For those patients with persistent abnormal serum hCG level and negative chest X-ray, chest CT scan is strongly recommended to identify the persist or resistant lung lesions and follow up.

EMA/CO regimen for chemotherapy 24 patients with ultra high-risk gestational trophoblastic neoplasia

Objective: To evaluate etoposide, methotrexate and dactinomycin (EMA) /cyclophosphamide and vincristine (CO) regimen for treatment of ultra high-risk gestational trophoblastic neoplasia (GTN) . Methods: A total of twenty-four ultra high-risk patients who had International Federation of Gynecology and Obstetrics (FIGO) prognostic scores greater or equal to 12 with liver, brain, or extensive metastases did poorly when treated with primary chemotherapy admitted in Women's Hospital, School of Medicine, Zhejiang University from January 2001 to December 2015. All of the patients were treated by EMA/CO regimen and followed up to death or December 2017. The clinical data of patients were analyzed retrospectively and the efficacy and toxicity of EMA/CO were evaluated. Results: All of the cases with ultra high-risk GTN had FIGO prognostic scores ≥12 (ranged 12-18, median 13.0) . Twenty patients (83%, 20/24) received EMA/CO regimen as primary treatment and 4 patients (17%, 4/24) had a history of failed chemotherapy. Seven patients (29%, 7/24) had metastasis of liver or brain and 17 patients (71%, 20/24) had no metastasis of liver and brain. Twenty-four patients received totally 167 courses of EMA/CO regimen (average 7.0 courses) . Sixteen patients achieved complete remission and 8 patients showed drug-resistant. The complete remission rate was 67% (16/24) and the resistance rate was 33% (8/24) . Of the 16 patients who got complete remission, 6 cases were treated with EMA/CO regimen alone, and 10 cases were treated by chemotherapy combined with surgery. For the 8 patients who showed drug-resistant to EMA/CO, 5 cases of them received EMA/etoposide and cisplatin (EP) regimen and 3 cases got remission, 1 case received methotrexate, dactinomycin and cyclophosphamide (MAC) regimen and got remission, 2 cases gave up treatment because of economic factors. The side effects of EMA/CO mainly included Ⅲ-Ⅳ degree neutropenia, anemia and alopecia. The incidence of Ⅲ-Ⅳ degree neutropenia during the treatment of EMA/CO was 21.6% (36/167) , the incidence of anemia was 96.4% (161/167) , and the incidence of alopecia was 60.5% (101/167) . In these 24 ultra high-risk GTN patients, 4 patients died during follow-up. In the 20 patients who got complete remission, no recurrence or secondary tumor by chemotherapy were occurred. Conclusion: EMA/CO is an effective regimen with manageable toxicity for patients with ultra high-risk GTN.

Salvage chemotherapy for gestational trophoblastic neoplasia: Utility or futility?

ObjectiveTo determine the efficacy of chemotherapy after failed initial treatment in patients with high risk gestational trophoblastic neoplasia (GTN). MethodsWe performed a retrospective IRB-approved chart review of all patients with GTN seen at a single institution from 1985 to 2015, including all patients who failed initial treatment. We summarized clinical characteristics with descriptive statistics and estimated progression-free survival (PFS) and overall survival (OS) with the Kaplan-Meier method. ResultsOf 68 identified patients, 38 required >2 chemotherapy regimens. Patients were treated for GTN (n=53), including choriocarcinoma, persistent GTN, and invasive mole; for placental site trophoblastic tumor (PSTT) (n=5); and for intermediate trophoblastic tumor (ITT) (n=10). Patients with GTN had a median of 2 salvage regimens, median PFS of 4.0months, and median OS was not reached at median follow-up of 71.2months. Active regimens included EMACO, MAC, BEP, platinum- and etoposide-based combination therapies, and ICE; 8 of 53 patients died of disease (DOD). Patients with PSTT had a median of 3 salvage regimens, median PFS of 2.8months, and median OS of 38.8months. Active regimens included ICE and EMA-EP; 4 of 5 patients DOD. Patients with ITT had a median of 3 salvage regimens, median PFS of 4.1months, and median OS of 38.2months. Active regimens included liposomal doxorubicin, platinum-containing regimens, EMA-CO, and EMA-EP; 7 of 10 patients DOD. ConclusionsSeveral salvage chemotherapy regimens demonstrate activity in high risk GTN. Multiple regimens may be required and cure is not universal.

Clinical characteristics and prognosis of ultra high-risk gestational trophoblastic neoplasia patients: A retrospective cohort study

ObjectiveThe gestational trophoblastic neoplasia (GTN) patients with the International Federation of Gynecology and Obstetrics (FIGO) score≥12 are defined as ultra high-risk GTN. This study aims to investigate the clinical characteristics, the treatment efficiency, and the prognosis of ultra high-risk GTN patients. MethodsBetween January 2002 and December 2015, medical record data of 143 GTN patients with FIGO score≥12 at Peking Union Medical College Hospital (PUMCH) were reviewed. Ratios were compared using chi-square test, and prognostic risk factors were analyzed by univariate analysis and multivariate analysis. ResultsAmong the 143 ultra high-risk GTN patients, 94 (65.7%) patients had achieved complete remission and 15.9% (15/94) patients relapsed after complete remission. The 5-year overall survival (OS) rate of the entire cohort approached 67.9%. The results of the multivariate analysis revealed that non-molar antecedent pregnancy [Relative risk (RR) 4.689, 95% CI 1.448–15.189, P=0.010], brain metastases (RR 2.280, 95% CI 1.248–4.163, P=0.007), previous failed multiagent chemotherapy (RR 5.345, 95% CI 2.222–12.857, P=0.000) and surgery (RR 0.336, 95% CI 0.177–0.641, P=0.001) all had influence on the prognosis of ultra high-risk GTN patients. ConclusionsGTN patients with FIGO score≥12 have a poor prognosis. More emphasis should be placed on non-molar antecedent pregnancy, brain metastases, and previous multiagent chemotherapy failure. Moreover, salvage surgery may improve the prognosis. Floxuridine-based multiagent chemotherapy is effective with manageable toxicity for ultra high-risk GTN patients.

Gestational Trophoblastic Disease: Opportunities for a National Registry Collaboration.

In rare entities such as gestational trophoblastic disease (GTD), only multi-institutional registries can gather significant number of patients to build up valuable clinical databases. No Canada-wide GTD registry currently exists. We conducted a survey among members of the Canadian Society of Gynecologic Oncology (GOC) to investigate their interest in a pan-Canadian GTD registry. We also took the opportunity to explore their management of GTD. An electronic survey was conducted. The target group was the entire GOC Canadian Membership. The survey consisted of 25 questions. The survey participation rate was 39% (67/171). Seventy-six percent of responders treat patients with molar pregnancy or gestational trophoblastic neoplasia (GTN), and the majority treat only 5 or less cases of molar pregnancy and 5 or less cases of GTN per year. In cases of low-risk GTN, 80% of responders use generally recommended single-agent chemotherapy regimens. In cases of high-risk GTN, 76% use generally recommended multiagent chemotherapy regimens. Most respondents do not submit either molar pregnancy or GTN patients to any formal registry, although the vast majority (92%) would do so if they had access to a registry, given that most believe that a registry can or probably can help patients with GTD. Responders indicated that the jurisdiction of such a registry should be national (59%), provincial (25%), and regional (11%). Despite some variation, responders were generally knowledgeable about contemporary management issues. Canadian Society of Gynecologic Oncology members acknowledge generally low exposure to GTD patients in Canada and support the creation of a national GTD registry to facilitate optimal patient care, education, and research.

Pulmonary Resection in the Management of High-Risk Gestational Trophoblastic Neoplasia.

The aim of this study was to evaluate the role of pulmonary resection in the management of high-risk gestational trophoblastic neoplasia (GTN). Patients who underwent pulmonary resection as part of their treatment for chemotherapy-resistant high-risk GTN from 1986 and 2014 were retrospectively analyzed. All patients had received 1 or more multiagent chemotherapy regimens preoperatively. Patient and disease characteristics were evaluated with respect to outcome. Fifteen (26%) of 58 patients treated for high-risk GTN underwent pulmonary resection with curative intent. Mean age of patients was 29 years (range, 19-37 years). International Federation of Gynecology and Obstetrics stage was III in 12 and IV in 3. International Federation of Gynecology and Obstetrics scores ranged from 5 to 20 (mean, 10). Antecedent pregnancy was nonmolar in 11 patients (73%). Adjuvant surgical procedures other than pulmonary resection were performed in 8 patients (53%). Preoperative chemotherapy regimens ranged from 1 to 10 (median, 4) and courses numbered from 2 to 32 (median, 14). Preoperative human chorionic gonadotropin (hCG) levels ranged from 2 to 2786 mIU/mL (median, 177 mIU/mL). Pulmonary wedge resections or lobectomies were performed via video-assisted thoracoscopic surgery (11) or thoracotomy (4). Two patients underwent pulmonary resections on 2 separate occasions. No patient had complications as a result of these procedures. Eleven patients (73%) were cured. In these 11 patients, hCG levels decreased to less than 2 mIU/mL within 6 to 52 days (mean, 22 days) postoperatively. Pulmonary resection of chemotherapy-resistant GTN was an important component of treatment in 26% of high-risk patients, 73% of whom were cured. Ideal candidates have disease isolated to the lungs and low hCG levels.

The effect of distance traveled on disease outcomes in gestational trophoblastic neoplasia

Gestational trophoblastic neoplasia is a rare gynecological malignancy often treated at tertiary referral centers. Patients frequently travel long distances to obtain care for gestational trophoblastic neoplasia, which may affect cancer outcomes in these patients. We examined the association between distance traveled to obtain care and disease burden at time of presentation as well as recurrence. We performed a retrospective cohort analysis of all patients diagnosed with gestational trophoblastic neoplasia from January 1995 to June 2015 at a high-volume tertiary referral center. Patients were included if they met International Federation of Gynecologyand Obstetrics 2000 criteria for postmolar gestational trophoblastic neoplasia or had choriocarcinoma, placental-site trophoblastic tumor, or epithelioid trophoblastic tumor. Sixty patients were identified. Disease burden at presentation was examined using both the World Health Organization prognostic score and International Federation of Gynecology and Obstetrics. Patients who traveled more than 50 miles were considered long-distance travelers based on previous literature on the effect of distance traveled on cancer outcomes.Demographic, clinical, and pathological data were obtained by chart review. Bivariable comparisons were performed using the χ(2) test or Fisher exact test for categorical variables. The t test or Wilcoxon rank-sum test was used to compare continuous variables when normallyor not normally distributed. Most patients presented at stage I (61%) with low-risk gestational trophoblastic neoplasia (70%). Median distance to care was 40 miles (range, 4-384). Eighteen patients (30%) had no insurance and 42 (70%) had either private or public insurance. Patients traveling more than 50 miles for care were more likely to have high-risk gestational trophoblastic neoplasia (46% vs 19%, P= .03), but there was no differencein recurrence (13% vs 11%, P= .89). Patients with high-risk gestational trophoblastic neoplasia lived 63miles farther (92 vs 28 miles, P < .001) than patients with low-risk gestational trophoblastic neoplasia. Long-distance travelers had a longer period between antecedentpregnancy and gestational trophoblastic neoplasia diagnosis (10 weeks vs 4.5 weeks, P= .009) and were more likely to receive multiagent chemotherapy (86% vs 61%, P=.03). In this cohort, long distance traveled to obtain care for gestational trophoblastic neoplasia was associated with an increased risk of presenting with high-risk disease and requiring multiagent chemotherapy for treatment. Patients with high-risk gestational trophoblastic neoplasia traveled nearly 100 miles to obtain care. There may be a delay in diagnosis in women traveling more than 50 miles to obtain care; however, we found no difference in recurrence risk for long-distance travelers.

Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia.

Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic. To determine which chemotherapy regimen/s for the treatment of resistant or relapsed GTN is/are the most effective and the least toxic. We searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 4), MEDLINE and EMBASE up to October 2011. In addition, we handsearched the relevant society conference proceedings and study reference lists. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to 16 Novemeber 2015. In addition, we searched online clinical trial registries for ongoing trials. Only randomised controlled trials (RCTs) were included. We designed a data extraction form and planned to use random-effects methods in Review Manager 5.1 for meta-analyses. The search identified no RCTs; therefore we were unable to perform any meta-analyses. RCTs in GTN are scarce owing to the low prevalence of this disease and its highly chemosensitive nature. As chemotherapeutic agents may be associated with substantial side effects, the ideal treatment should achieve maximum efficacy with minimal side effects. For methotrexate-resistant or recurrent low-risk GTN, a common practice is to use sequential five-day dactinomycin, followed by MAC (methotrexate, dactinomycin, cyclophosphamide) or EMA/CO (etoposide, methotrexate, dactinomycin, cyclophosphamide, vinblastine) if further salvage therapy is required. However, five-day dactinomycin is associated with more side effects than pulsed dactinomycin, therefore an RCT comparing the relative efficacy and safety of these two regimens in the context of failed primary methotrexate treatment is desirable.For high-risk GTN, EMA/CO is the most commonly used first-line therapy, with platinum-etoposide combinations, particularly EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin), being favoured as salvage therapy. Alternatives, including TP/TE (paclitaxel, cisplatin/ paclitaxel, etoposide), BEP (bleomycin, etoposide, cisplatin), FAEV (floxuridine, dactinomycin, etoposide, vincristine) and FA (5-fluorouracil (5-FU), dactinomycin), may be as effective as EMA/EP and associated with fewer side effects; however, this is not clear from the available evidence and needs testing in well-designed RCTs. In the UK, an RCT comparing interventions for resistant/recurrent GTN will be very challenging owing to the small numbers of patients with this scenario. International multicentre collaboration is therefore needed to provide the high-quality evidence required to determine which salvage regimen/s have the best effectiveness-to-toxicity ratio in low- and high-risk disease. Future research should include economic evaluations and long-term surveillance for secondary neoplasms.

Fatal Cases of Gestational Trophoblastic Neoplasia in a National Trophoblastic Disease Reference Center in Dakar Senegal.

The objectives of this study were to analyze deaths after gestational trophoblastic neoplasia and to determine the factors of treatment failure. This is a retrospective study in Aristide Le Dantec teaching Hospital in Dakar, Senegal, between 1 January 2006 and 31 December 2014. We took into account socio-epidemiological characteristics of patients, initial diagnosis, time between uterine evacuation and admission, time to onset of gestational trophoblastic neoplasia (GTN), treatment received (deadlines, protocols), difficulties experienced in the diagnosis and the initiation of treatment and survival. In total, 1044 patients were admitted during the study period; 164 cases of GTN were diagnosed (15.7%); and 21 deaths occurred leading to a specific lethality of 12.8%. The average age was 30 years. Almost all patients (n = 18; 85.7%) had low income or no income. Eight out of 21 patients (38.1%) were seen in our department after GTN onset. The mean time to onset of GTN of all patients was 22.1 weeks. For 66.6%, histology was not available; the diagnosis of hydatidiform mole was made on the clinical history and sonographic features and GTN on human chorionic gonadotrophin (hCG) evolution and ultrasound findings. None of the patients had regular chemotherapy due to financial reasons. Patients who died within 3 months after diagnosis had metastatic tumors (7 of 21). All these women had resistance to treatment or progressed after three courses of chemotherapy. Ten of the 12 women with high-risk GTN were not treated with multi-agent chemotherapy (EMA-CO) for purely financial reasons. The high incidence and mortality require a profound reorganization of our health system and a high awareness of practitioners to refer to time or to declare all suspected cases of hydatidiform mole or gestational trophoblastic neoplasia.

Refractory Gestational Trophoblastic Neoplasia: A Novel Drug Combination With Paclitaxel and Carboplatin Produces Durable Complete Remission.

The aim of this study was to evaluate the results with novel drug combination consisting of paclitaxel and carboplatin (PC) for salvage of refractory high-risk gestational trophoblastic neoplasia (GTN) previously treated with EMA-CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristine) and EMA-EP (etoposide, methotrexate, actinomycin, and cisplatin) regimens. This was a prospective study conducted at a regional cancer institute from 2008 to 2012. The study group received the combination of paclitaxel (175 mg/m) and carboplatin (area under the curve, 6) intravenously every 3 weeks. After undetectable β-subunit of human chorionic gonadotropin values are achieved, 2 courses of additional chemotherapy were administered to reduce the risk of relapse. They were followed up and assessed by clinical examination, monthly β-subunit of human chorionic gonadotropin for a minimum of 24 months. The event-free survival and overall survival were calculated for all patients using Kaplan-Meier curve (SPSS version 19; SPSS Inc). A total of 65 persistent GTN patients were treated during the study period. Eight (12.3%) of 65 patients having refractory GTN were treated with PC regimen. The initial International Federation of Gynecology and Obstetrics staging in the study group was stage I disease in 1 (12.5%), stage III in 4 (50%), and stage IV in 3 (37.5%) patients. According to the World Health Organization prognostic risk scores, 1 patient was in the low-risk group (12.5%), and 7 patients were in the high-risk group (87.5%). The study group received a total 35 courses of the combination PC. The median number of courses for each patient was 4.4. The complications include mucositis in 3 patients and thrombocytopenia, febrile neutropenia, and transient hepatic dysfunction in other patients. Six (75%) of 8 patients had good response, whereas 2 patients had progression. Five patients (62.5%) are in remission at median 30 months' follow-up, and 3 (37.5%) of 8 patients have died. The combination of paclitaxel and carboplatin (PC) regimen produces durable complete remission and manageable side effect profile in patients with refractory GTN previously treated extensively with frontline chemotherapies.

Mortality rate of gestational trophoblastic neoplasia with a FIGO score of ≥13

Gestational trophoblastic diseases include premalignant (partial and complete hydatidiform moles) and malignant entities referred to as gestational trophoblastic neoplasia. Use of the International Federation of Gynecology and Obstetrics prognostic score is encouraged in cases of gestational trophoblastic neoplasia to predict the potential for the development of resistance to single-agent chemotherapy. An International Federation of Gynecology and Obstetrics score of ≥7 defines a high-risk patient and requires combination chemotherapy. Appropriate and rapid diagnosis, treatment by specialized centers, and reduction of early deaths at the time of chemotherapy initiation have led to significant improvements in survival for patients with high-risk gestational trophoblastic neoplasia. There is a crucial need for the early identification of high-risk patients with gestational trophoblastic neoplasia who have an increased death risk to organize their treatment in highly specialized centers. The purpose of this study was to describe cases of gestational trophoblastic neoplasia that have resulted in death, particularly in a subgroup with an International Federation of Gynecology and Obstetrics prognostic score of ≥13, for whom low-dose etoposide and cisplatin induction chemotherapy recently was shown to reduce early death rate. We identified 974 patients from the French Center for Trophoblastic Diseases who had a diagnosis of gestational trophoblastic neoplasia from November 1999 to March 2014. Among 140 patients who were at high risk of resistance to single-agent chemotherapy (International Federation of Gynecology and Obstetrics score, ≥7), 29 patients (21%) had a score of ≥13. Mortality rate was estimated with the use of the Kaplan-Meier method. The 5-year overall mortality rate, after the exclusion of placental site trophoblastic tumors and epithelioid trophoblastic tumors, was 2% for patients with gestational trophoblastic neoplasia (95% confidence interval, 1.25-3.13%). High-risk patients had a 5-year mortality rate of 12% (95% confidence interval, 7.49-18.9%). Patients with an International Federation of Gynecology and Obstetrics score of ≥13 had a higher 5-year mortality rate (38.4%; 95% confidence interval, 23.4-58.6%) and accounted for 52% of the deaths in the entire cohort. Early deaths, defined as those that occur within 4 weeks after treatment initiation, occurred in 8 patients of the entire cohort. Six of them had an International Federation of Gynecology and Obstetrics score of ≥13 at presentation, of whom 5 patients had brain and/or liver metastases. Gestational trophoblastic diseases with an International Federation of Gynecology and Obstetrics score of ≥13 have an increased risk of early death. We suggest that an International Federation of Gynecology and Obstetrics score of ≥13 becomes a consensual criterion for prediction of patients with gestational trophoblastic neoplasia with increased risk of death, particularly early death. These patients justify treatment in highly specialized gestational trophoblastic disease centers and may benefit from the use of induction low-dose etoposide and cisplatin.

Human Chorionic Gonadotropin (hCG) Regression Curve for Predicting Response to EMA/CO (Etoposide, Methotrexate, Actinomycin D, Cyclophosphamide and Vincristine) Regimen in Gestational Trophoblastic Neoplasia.

An hCG regression curve has been used to predict the natural history and response to chemotherapy in gestational trophoblastic disease. We constructed hCG regression curves in high-risk gestational trophoblastic neoplasia (GTN) treated with EMA/CO and identified an optimal hCG level to detect EMA/CO resistance in GTN. Eighty-one women with GTN treated with EMA/CO were classified as primary high-risk GTN (n=65) and single agent-resistance GTN (n=16). The hCG levels prior to each course of chemotherapy were plotted in the 10th, 50th, and 90th percentiles to construct the hCG regression curves. Diagnostic performance was evaluated for an optimal cut-off value. The median hCG levels were 264,482 mIU/mL mIU/mL and 495.5 mIU/mL mIU/mL for primary high-risk GTN and single agent-resistance GTN, respectively. The 50th percentile of the hCG level in primary high-risk GTN and single agent-resistance turned to normal before the 4th and the 2nd course of chemotherapy, respectively. The 90th percentile of the hCG level in primary high-risk GTN and single agent-resistance turned to normal before the 9th and the 2nd course of chemotherapy, respectively. The hCG level of ≥118.6 mIU/mL mIU/mL at the 5thcourse of EMA/CO predicted the EMA/CO resistance in primary high-risk GTN patients with a sensitivity of 85.7% and a specificity of 100%. EMA/CO resistance in primary high-risk GTN can be predicted by using an hCG regression curve in combination with the cut-off value of 118.6 mIU/mL at the 5thcourse of chemotherapy.

Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors

To investigate the slope of linear regression of postevacuation serum hCG as an independent risk factor for postmolar gestational trophoblastic neoplasia (GTN). Multicenter retrospective cohort study. Academic referral health care centers. All subjects with confirmed hydatidiform mole and at least four measurements of β-hCG titer. None. Type and magnitude of the relationship between the slope of linear regression of β-hCG as a new risk factor and GTN using Bayesian logistic regression with penalized log-likelihood estimation. Among the high-risk and low-risk molar pregnancy cases, 11 (18.6%) and 19 cases (13.3%) had GTN, respectively. No significant relationship was found between the components of a high-risk pregnancy and GTN. The β-hCG return slope was higher in the spontaneous cure group. However, the initial level of this hormone in the first measurement was higher in the GTN group compared with in the spontaneous recovery group. The average time for diagnosing GTN in the high-risk molar pregnancy group was 2 weeks less than that of the low-risk molar pregnancy group. In addition to slope of linear regression of β-hCG (odds ratio [OR], 12.74, confidence interval [CI], 5.42-29.2), abortion history (OR, 2.53; 95% CI, 1.27-5.04) and large uterine height for gestational age (OR, 1.26; CI, 1.04-1.54) had the maximum effects on GTN outcome, respectively. The slope of linear regression of β-hCG was introduced as an independent risk factor, which could be used for clinical decision making based on records of β-hCG titer and subsequent prevention program.

Pulmonary resection in the treatment of high-risk gestational trophoblastic neoplasia

Pulmonary resection in the treatment of high-risk gestational trophoblastic neoplasia

Cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, and vincristine in the treatment of gestational trophoblastic neoplasia.

The aim of this study was to evaluate the efficacy and toxicity profile of the cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, and vincristine (CHAMOC) regimen in the treatment of high-risk gestational trophoblastic neoplasia (GTN). We conducted a retrospective study of all patients with GTN treated with the CHAMOC regimen between 1985 and 2012 in a tertiary referral center in Hong Kong. Medical records were reviewed, and data were analyzed. Response rate and toxicity profile were assessed. The CHAMOC regimen was given to 79 patients from 1985 to 2012, with a total of 388 cycles administered. Among the 79 patients, CHAMOC was given to 68 as the primary treatment of high-risk GTN, whereas it was used as the salvage chemotherapy in 11 patients for failure with other chemotherapy regimens or recurrent disease. Complete remission was achieved in 58 patients (85.3%) in the primary treatment group and 8 patients (72.7%) in the salvage treatment group. Grade 3 and grade 4 neutropenia were observed in 13.0% and 3.4% of the chemotherapy cycles, respectively. Grade 3 or 4 thrombocytopenia was rare (1.3% of all treatment cycles). No secondary malignancy was observed in our patients with a mean duration of follow-up of 9.7 to 13 years, except 1 patient with advanced colon cancer diagnosed shortly after chemotherapy, which was unlikely to represent a secondary malignancy from the chemotherapy. The CHAMOC regimen should be considered as an alternative to other chemotherapy regimens in the primary treatment of high-risk gestational trophoblastic disease, with comparable efficacy, similar short-term side-effects profile, and potentially fewer long-term complications.

Diagnosis, classification and treatment of gestational trophoblastic neoplasia.

Gestational trophoblastic neoplasia (GTN) is the term to describe a set of malignant placental diseases, including invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Both invasive mole and choriocarcinoma respond well to chemotherapy, and cure rates are greater than 90%. Since the advent of chemotherapy, low-risk GTN has been treated with a single agent, usually methotrexate or actinomycin D. Cases of high-risk GTN, however, should be treated with multiagent chemotherapy, and the regimen usually selected is EMA-CO, which combines etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine. This study reviews the literature about GTN to discuss current knowledge about its diagnosis and treatment.